title: Common variants in the JAZF1 gene associated with height identified by linkage and genome-wide association analysis.
abstract: Genes for height have gained interest for decades, but only recently have candidate genes started to be identified. We have performed linkage analysis and genome-wide association for height in approximately 4000 individuals from five European populations. A total of five chromosomal regions showed suggestive linkage and in one of these regions, two SNPs (rs849140 and rs1635852) were associated with height (nominal P = 7.0 x 10(-8) and P = 9.6 x 10(-7), respectively). In total, five SNPs across the genome showed an association with height that reached the threshold of genome-wide significance (nominal P < 1.6 x 10(-7)). The association with height was replicated for two SNPs (rs1635852 and rs849140) using three independent studies (n = 31 077, n=1268 and n = 5746) with overall meta P-values of 9.4 x 10(-10) and 5.3 x 10(-8). These SNPs are located in the JAZF1 gene, which has recently been associated with type II diabetes, prostate and endometrial cancer. JAZF1 is a transcriptional repressor of NR2C2, which results in low IGF1 serum concentrations, perinatal and early postnatal hypoglycemia and growth retardation when knocked out in mice. Both the linkage and association analyses independently identified the JAZF1 region affecting human height. We have demonstrated, through replication in additional independent populations, the consistency of the effect of the JAZF1 SNPs on height. Since this gene also has a key function in the metabolism of growth, JAZF1 represents one of the strongest candidates influencing human height identified so far.
authors.affiliation: Rudbeck Laboratory, Department of Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden.
authors.forename: Asa
authors.initials: A
authors.lastname: Johansson
authors.forename: Fabio
authors.initials: F
authors.lastname: Marroni
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Franklin
authors.forename: Anatoly V
authors.initials: AV
authors.lastname: Kirichenko
authors.forename: Inger
authors.initials: I
authors.lastname: Jonasson
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Hicks
authors.forename: Veronique
authors.initials: V
authors.lastname: Vitart
authors.forename: Aaron
authors.initials: A
authors.lastname: Isaacs
authors.forename: Tatiana
authors.initials: T
authors.lastname: Axenovich
authors.forename: Susan
authors.initials: S
authors.lastname: Campbell
authors.forename: Malcolm G
authors.initials: MG
authors.lastname: Dunlop
authors.forename: Jamie
authors.initials: J
authors.lastname: Floyd
authors.forename: Nick
authors.initials: N
authors.lastname: Hastie
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Sara
authors.initials: S
authors.lastname: Knott
authors.forename: Ivana
authors.initials: I
authors.lastname: Kolcic
authors.forename: Irene
authors.initials: I
authors.lastname: Pichler
authors.forename: Ozren
authors.initials: O
authors.lastname: Polasek
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Albert
authors.initials: A
authors.lastname: Tenesa
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Wild
authors.forename: Irina V
authors.initials: IV
authors.lastname: Zorkoltseva
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: James F
authors.initials: JF
authors.lastname: Wilson
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Cristian
authors.initials: C
authors.lastname: Pattaro
authors.forename: Peter
authors.initials: P
authors.lastname: Pramstaller
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Yurii S
authors.initials: YS
authors.lastname: Aulchenko
authors.forename: Ulf
authors.initials: U
authors.lastname: Gyllensten
mesh_terms: D001827:Body Height / Q000235:genetics*; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D005260:Female; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C430460:JAZF1 protein, human; D009363:Neoplasm Proteins